Research press release


Nature Medicine

Vaccine mystery solved



F Polackたちは、ウイルスに対する防御効果が得られなかったのは、防御抗原に対する抗体の親和性が低かったためであることを明らかにした。病原体検出に重要な役割を果たす免疫分子、Toll様受容体(TLR)への刺激が乏しいために、抗体の成熟がうまく起こらなかったのである。機能しなかったワクチンと一緒にTLR活性化因子をマウスに接種したところ、RSVに対する防御効果が得られた。


In the 1960s, a vaccine against the respiratory syncytial virus (RSV) mysteriously failed to protect children and even made the disease worse. An article in Nature Medicine this week reports data that explain this mystery 40 years later.

RSV?the agent that causes bronchiolitis?is a leading cause of hospitalization in infants worldwide. Over 40 years ago, a formalin-inactivated RSV vaccine was used to immunize children, but it failed to provide protection from the virus and even led to severe disease. A widely accepted explanation for the vaccine’s failure was that formalin disrupted protective antigens?portions of the virus that should have induced the production of protective antibodies.

Fernando Polack and his colleagues now show that the lack of protection was due instead to low antibody affinity for the protective antigens. The maturation of the antibodies was impaired by poor stimulation of Toll-like receptors (TLRs)?immune molecules key for the detection of pathogens. When the authors gave a TLR activator together with a failed vaccine to mice, the mixture provided protection from RSV.

The study explains why the inactivated vaccine did not protect the children, hampering RSV vaccine development for four decades. It also suggests that inactivated RSV vaccines may be rendered effective by inclusion of TLR agonists in their formulation, and it identifies affinity maturation as a key factor for the safe immunization of infants.

doi: 10.1038/nm.1894


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